The Journal of Experimental Medicine
Torrey Pines Biolabs
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
This Article
Right arrow Full Text
Right arrow Full Text (PDF, 154K)
Right arrow PPT slides of all figures
Right arrow Alert me when this article is cited
Right arrow Citation Map
Services
Right arrow Email this article
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new content in the JEM
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Yeh, J.-H.
Right arrow Articles by Lai, M.-Z.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Yeh, J.-H.
Right arrow Articles by Lai, M.-Z.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Facebook   Add to Reddit   Add to Technorati   Add to Twitter  
What's this?
© The Rockefeller University Press, 0022-1007/1998/11/1795/ $5.00
The Journal of Experimental Medicine, Volume 188, Number 10, November 16, 1998 1795-1802

Articles

Mitogen-activated Protein Kinase Kinase Antagonized Fas-associated Death Domain Protein–mediated Apoptosis by Induced FLICE-inhibitory Protein Expression

Jung-Hua Yeh*,{ddagger}, Shu-Ching Hsu{ddagger},§, Shou-Hwa Han*, and Ming-Zong Lai*,{ddagger},§

From the * Graduate Institute of Microbiology and Immunology, National Yang-Ming University, Taipei 11217, Taiwan; the {ddagger} Institute of Molecular Biology, Academia Sinica, Nankang, Taipei 11529, Taiwan; and the § Graduate Institute of Microbiology, National Taiwan University School of Medicine, Taipei 10018, Taiwan

Fas and Fas-associated death domain (FADD) play a critical role in the homeostasis of different cell types. The regulation of Fas and FADD-mediated cell death is pivotal to many physiological functions. The activation of T lymphocytes by concanavalin A (Con A) inhibited Fas-mediated cell death. We identified that among the several activation signals downstream of Con A stimulation, mitogen-activated protein (MAP) kinase kinase (MKK) was the major kinase pathway that antagonized Fas-triggered cell death. MKK1 suppressed FADD- but not caspase-3– induced apoptosis, indicating that antagonism occurred early along the Fas-initiated apoptotic cascade. We further demonstrated that activation of MKK1 led to expression of FLIP, a specific inhibitor of FADD. MKK1 inhibition of FADD-induced cell death was abrogated if induction of FLIP was prevented, indicating that FLIP mediates MKK1 suppression of FADD-mediated apoptosis. Our results illustrate a general mechanism by which activation of MAP kinase attenuates apoptotic signals initiated by death receptors in normal and transformed cells.

Key Words: mitogen-activated protein kinase kinase • Fas-associated death domain protein • Fas • FLIP • apoptosis

Address correspondence to Ming-Zong Lai, Institute of Molecular Biology, Academia Sinica, Nankang, Taipei 11529, Taiwan, Republic of China. Phone: 886-2-2789-9236; Fax: 886-2-2782-6085; E-mail: mblai{at}ccvax.sinica.edu.tw

This project was supported by grant DOH86-HR-508 from the Department of Health, grant NSC 86-2316-B001-012 M30 from the National Science Council, and a grant from Academia Sinica.

Abbreviations used: DR, death receptor; FADD, Fas-associated death domain protein; FLICE, FADD-like ICE; FLIP, FLICE-inhibitory protein; ICE, IL-1β–converting enzyme; MAPK, mitogen-activated protein kinase; MKK, MAPK kinase; nt, nucleotide(s); PI, propidium iodide; RT, reverse transcription.


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Facebook Facebook   Add to Reddit Reddit   Add to Technorati Technorati   Add to Twitter Twitter    What's this?


This article has been cited by other articles:



  Home | Help | Feedback | Subscriptions | Archive | Search
TABLE OF CONTENTS